Exploring Diverse Avenues of Income for Clinical Researchers

In the ever-evolving landscape of professional opportunities, the dream of earning from multiple sources has become a reality for a fortunate few. Clinical research, a field known for its dynamism, opens doors to an array of income streams that can be harnessed based on educational background, skill set, and experiences. Leveraging online platforms has further broadened the horizons for clinical researchers, enabling them to tap into various opportunities despite constraints.

Unveiling Lucrative Avenues

Medical Writing: Medical writing is a versatile domain that offers an array of roles. From drafting research proposals, summaries of product characteristics (SMPCs), safety reports, to crafting content for medical journals, health magazines, or websites, the opportunities are diverse. Clinical researchers can venture into protocol writing, investigator's brochures, informed consent forms, and trial reports. Flexibility is key here; one can be employed full-time, on a contract basis, or as a consultant, optimizing their skills and time while working from the comfort of their own space.

Data Management: Clinical data management, a pivotal aspect of clinical trials, presents an array of roles. Proficiency in basic data handling tools such as Excel and SPSS is essential. More complex trials may necessitate skills in software like SAS and R. Clinical researchers adept at working with data can engage in data entry, cleaning, and analysis, optimizing their contribution to the research process.

Phase I Clinical Trials: Phase I trials, involving healthy volunteers, offer an opportunity for clinical researchers seeking unconventional working hours. With stringent monitoring requirements, these trials often require staffing around the clock. For those with daytime commitments, engaging in phase I trials during mornings, evenings, or night shifts can prove to be a lucrative option.

Registry Involvement: With a solid foundation in research methodology, data management, and medical terminology, clinical researchers can expand their horizons by participating in disease registries and clinical trial databases. Playing a vital role in registering trials and maintaining databases, these experts facilitate both sponsors and registry platforms. Engaging with disease-specific or global registries can open doors to consistent income streams.

Project Set Up: Setting up project environments and managing clinical trial sites require a unique set of skills. Clinical researchers familiar with study site dynamics and experienced in project setup can contribute significantly. Handling logistical aspects, regulatory compliance, and site management, these professionals ensure smooth trial operations. With expertise, they can juggle multiple trials simultaneously, enhancing their earning potential.

Consulting Services: Providing consulting services to sponsors and Contract Research Organizations (CROs) offers a pathway to diversified income. Assisting foreign sponsors in navigating local environments for global trials or aiding pharmaceutical companies in pharmacovigilance post-product launch, clinical researchers can capitalize on their expertise and offer invaluable insights.

Conclusion: Embracing a Multifaceted Future

Clinical research professionals possess a unique skill set that allows them to explore a range of income-generating opportunities. As the field evolves and globalizes, the potential for diverse roles only expands. Embracing digital platforms and leveraging specialized skills can empower clinical researchers to seize multiple streams of income, transforming their professional journey into one of both financial stability and personal fulfillment.

So, whether you're a seasoned clinical researcher or an aspiring one, the world of clinical research is brimming with income-generating prospects. By aligning your expertise with the right opportunity, you can craft a rewarding and multifaceted career in this dynamic field.

Thank you for reading!

Urgent Need of Contract Research Organization (CRO) in Nepal

Nepal is currently facing a huge shortage of job opportunity leading to an incremental brain drainage from the country. All the faculties of educations are victims of this problem and same is the situation for clinical researchers and pharmacist. Working in the field of clinical research needs multiple expertise like sound knowledge of diseases, available treatment / therapies, research methodology, biostatistics, clinical operations and many more technical information along with organizational culture and teamwork skills. A well-functioning CRO can provide job opportunity and career growth platform to exercise all of these aspects for a clinical research aspirant. 

Let us understand first about how a CRO functions in a brief. A CRO always conducts research for other companies on a contract basis. Any pharmaceutical or biomedical or biotechnology based medical device company will prepare their product by performing drug development and early phase research. A CRO will take their product and perform clinical trial leading to regulatory approval of that particular candidate so that it can go to the market at the earliest.  

Why Nepal Needs a CRO?

There are many reasons why such organization should be established as soon as possible. I have enlisted few of them below: 

1. Creating more job opportunities:

There is extreme lack of job opportunity for various medical professionals such as doctors, nurses, pharmacist and other auxiliary health professionals despite good competency on the subject matter. A contract Research Organization is definitely a good platform for all of the professionals in terms of experience as well as financial return. 

2. Performing BPO: 

Since CRO works in the contract basis with other pharma or biotechnological organization, they can outsource any or all of their work anywhere in the world based upon the need by business process outsourcing (BPO) method; companies do not have to conduct research in Nepal by itself, but they can outsource the work from other countries to here in Nepal and pay as per the work on need basis. Suh work can be performed from home as well as office, which means it is an opportunity for a working professional to earn their extra income and also for people who want to work remotely from anywhere from the country. 

3. Opportunity to conduct large - scaled trials in the country

A CRO not only works on the basis of business process outsourcing (BPO), but also conduct research / trials on its own. In Nepal, we have enough hospitals and healthcare professionals but till date all the clinical trials that are being conducted are designed in some other countries and we are working just as data collectors. In future, if any vaccine candidates have to go through clinical trials, we can take up their product and conduct clinical trial on our own environment. Necessary skilled human resources will be produced from the corporations with enough of exposure on their respective fields.

4. Positive Impact on the country's economy: 

Since we are on or below poverty line as per economic parameters and running out of foreign currency reserve due to very wide trade deficit, a large-scaled companies running within the country and bringing money into the economy from outside world is of utmost importance for the economy to function better. Quantitatively if a CRO functions well in the Nepal, government can benefit directly from taxation and bringing foreign currency into the Nepalese economy. But on wider view, positive impacts are much more and qualitative in nature. These can be listed in terms of payment scale, lifestyle, work culture, exposure and skills enhancement, personal development, fostering local businesses, tourism enhancement and for creating positive environment within the country so that upcoming generations can see their future in their own country. 

If you also have some ideas to share regarding this topic, please feel free to comment below

                                                                                        

                                                                                                Thank You!!!

Advancing Clinical Research in Nepal: Urgent Calls for Regulatory Framework Upgrades

In recent days, Nepal has been involved in a number of clinical trials specially after the hit of COVID-19 pandemic. Most of such trials were developed on some other countries, imported and implemented here in Nepal. Rise of COVID-19 has certainly given an opportunity for a burning mind of the country in order to involve in a global movement of developing a new therapy or vaccine. This movement has been facilitated from two major government organization - Nepal Health Research Council (NHRC) and Department of Drug Administration (DDA). But In order to make country self-dependent on developing and implementing new trials, there must be few upgrades in the regulation and infrastructure in both of these organizations. 

Nepal Health Research Council (NHRC) provides both ethical review support for all the trials registered and also acts as implementation body for any new trial conducted by or in collaboration with other organizations. In 2019, NHRC has published 'National Ethical Guideline for Health Research in Nepal' which provides direction to perform clinical trial activities anywhere within the country in the most ethical manner possible. All in one, NHRC works as regulatory body as well as implementation body combinedly. for this purpose, it has made collaborations with many national and international organizations working in the field of human health research such as Indian Council of Medical Research (ICMR), International Vaccine Institute (IVI), Oxford University Clinical Research Unit (OUCRU). 

Similarly, Department of Drugs Administration (DDA) is the national licensing authority of the country which reviews and authenticate the documents submitted by clinical trialist / individual or an institute. Based upon the favorable opinion and round of reviews, it provides certificate for conducting research. DDA approval is needed only if you are conducting trial / research on a specific drug or medications but not for other kind of therapies or observational research. After submitting documents physically to 'Administration' section, it will move to the respective department and reviewal process will start. There are multiple departments within DDA for different activities like registration of pharmaceutical company, a pharmacy, import / export of drugs, approval / registration of a medicine, registration of trial etc. 

Problems and Immediate Changes Needed in DDA 

• A new researcher coming to DDA in order to register his / her trial will demotivated by too many windows to queue, lots of Paperworks, ambiguous comments and lack of clarity among the review members themselves. But actually, review process is much simpler than it seems to be. In short, if review and approval process is made via online platform, all the activities will run smoothly in less time-consuming manner which will ease the whole process itself. Though DDA is the national regulatory authority where national as well as international delegates come for different purpose, DDA functions like any other government offices which should be changed immediately. Adapting online platform is mandatory for any office sooner or later. If appropriate arrangements are made in place needed to implement online registration, reviewal and approval process, research activities will be completed more smoothly. 

• Guideline and regulations should be updated enough to make them relevant with the time. Most of the legal obligation under which we are working currently are older than researcher themselves. Getting an approval and being regulated from those outdated guideline is another frustrating experience for a researcher. As for example, if you register a clinical trial which is adaptive in design, once the trial is approved and implemented, there might be multiple amendments to the protocol based upon current scenarios and the requirements. It is not possible to receive new approval license from DDA each time with the protocol amendment. DDA does not have such regulations in place to regulate such trials whereas adaptive design is the most commonly employed model of clinical trial throughout the world on recent times. Similar experiences are there with trials being conducted on emergency health situations like COVID-19 pandemics. 
• Other changes also carry some importance such as administrative, infrastructure wise and for smooth experience of visitors. Such arrangements may not directly affect much the integrity of the functions of DDA. 

                Immediate Changes Needed at Nepal Health Research Council (NHRC)  

Being a part of organization, I may be biased on reviewing functioning of Nepal Health Research Council (NHRC). If you are an independent researcher or have acquainted with the functions of NHRC from any other organizations, your review and experience will matter more than that of mine. Anyway, these are the changes that 'NHRC' should address at the earliest in order to foster research culture in Nepal. 

• Establishing an independent clinical research unit. A separate unit which is completely dedicated for reviewing new clinical trials proposals, conducting meetings and conferences with other different organizations for collaborations, continuation and daily implementation of the trials on the implementation phase and for capacity building of the clinical trials experts in the country. Such unit should be led by an expert working in relevant field. For clinical trial culture to foster in the country, it demands a lot of discussions, trainings and implementation. NHRC only can and should provide such platform for all the researcher working inside and out of the country. 
• Separating ethical review support from routine activities of NHRC. Since NHRC is working both as ethical review board as well as trial implementation body, there is chances of conflict of interest and functions of one can be hindered by the other. Ethical review board of NHRC should be independent not only on provision but also in physical and real sense. Ethical Review Board (ERB) and its activities must be independent from routine NHRC functions which includes multiple meetings, implementation of an observational trials, training and so on. All those activities will definitely hinder the ERB functions and international communities may not consider its activities with higher integrity. 
• Developing an online central information system. If any researcher working here in Nepal or any part of the world wants to make an query about the current situation of health research status or particular evidence, NHRC should be able to respond them online and such system has to be established available for public domain. All in all, NHRC should function as center of evidence generation and dissemination. 
• Strengthening research activities on other institutes. NHRC cannot and should not function all the health research activities on its own. Only if every medical college and hospitals of Nepal involve in evidence generation by themselves, research culture of the country will be upgraded. NHRC should be center of facilitation for other research institutes as well. 

If you have any other viewpoints about how research and clinical trials should be regulated / promoted in the country, please give your opinion on the comment box below.

                                                                        Many Thanks !!!!

PRECIS Tool - Critical Analysis to Pragmatic Trials

https://www.bmj.com/content/350/bmj.h2147

Pragmatic Explanatory Continuum Indicator    Summary (PRECIS) is the tool designed by clinical trials specialist in order to help other clinical trialist to design a trial that best fits on pragmatic platform. Since most of the pragmatic trials being implemented in the recent days are self-declared, their design and implementation may not best fit with the global standard set for conducting pragmatic trials. Here we will discuss about the PRECIS-2 tool and its different domains. 

History of PRECIS tool 

The original PRECIS tool was developed in 2005 - 2008 by 25 international trialists and methodologists with the prime objectives of helping other trial specialists to make their better decision while designing a trial by allowing them to test the questions they are seeking answer for. PRECIS tool was used widespread between 2009 to 2013 by various researchers. Later this tool received a lot of criticism for having unclear face validity, inter rater reliability, the lack of scoring system, redundancy in PRECIS domain etc. After addressing all of those criticism and comments, an updated version was released in 2013 with the name of PRECIS-2 tool. This updated version is still being used globally and been cited around 1100 times from https://www.bmj.com/content/350/bmj.h2147 as per Sep 2022. 

Domains of PRECIS-2 Tool 

There are nine different domains in the PRECIS-2 tool which help trialist to think of the trials design decision considering the future reproducibility of the trial result. 

     1. Eligibility

• Are Participants recruited in the trials similar to the future intended population? 
• Higher the similarity between the people in trials and those in usual care settings, higher the score would be. 
• Excluding people with less adherence to treatment, based on laboratory tests results, having less responsive to the treatment, excluding people who have difficulties in completion of trials like old, aged population and children 
• If Inclusion / Exclusion criteria is more stringent by including many laboratory tests before drug administration, trial will incline towards explanatory design from pragmatic one. 
• Highest score that trial will get from this criterial would be Five. 

     2. Recruitment

• Was there the similarity of effort being made to recruit participant with that for a patient to engage into the treatment process? 
• In an extremely pragmatic settings, patient will be informed of the study in usual care settings and recruitment will be made based upon their interest. 
• Sometimes an extra effort needs to be made by additional human resources or by enhancing knowledge about the trial among potential participants via different communication tools such as mailing invitations letters, Radio / Television advertisement etc. The only concern is potential participants should not be over influenced by the information provided.
• Recruitment from usual hospital settings without additional effort is scored as '5'. 

     3. Settings

• How similar / different is the trial settings from usual care?
• In this domain, trialists are encouraged to match their settings proposed for a clinical trial with the hospital setting where patients are being treated on regular basis. 
• While designing a pragmatic trial, various characteristics of a settings are to be considered such as: geography, healthcare system, socioeconomic and cultural background of that particular country / community and other nuances of the population trial is being intended to apply on. Higher the matching between them, trial will be considered more pragmatic. 
• Sometimes the same socioeconomic constrains of a particular setting can be of no issue rather supportive in different settings. 

     4. Organization

• How different are the resources, provide expertise and the organization of delivery in the intervention arm of the trial from those available in the usual care settings. 
• This domain specifically focuses on resources and human expertise available in a particular healthcare setting. If service provided to a trial participant is from highly skilled and trained personnel in well-equipped setting but regular visitors are not receiving the same degree of care and treatment from healthcare center, trial will lose its pragmatism and will incline towards being an explanatory. 
• A highly pragmatic trial will receive score '5' and highly explanatory one will receive score of '1'

     5. Flexibility (Delivery) 

• How flexibly intervention is being administered in trial setting than usual care setting. 
• In order to make a trial more pragmatic, trialist should anticipate the future of that particular intervention post trial in the same hospital / study site and the flexibility on how to introduce an intervention should be provided accordingly.
• If protocol does not dictate rigidly how to deliver an intervention for a trial participant, there will be similarity in the between patient admitted and treated in the hospital and the trial participants. The most flexible study will score maximum of '5' which means trial is most pragmatic. 
• If trialist wants study to be descriptive in nature, he should be very rigid about dose, time-schedule, person and method of delivery of that particular intervention. But this methodology will score the trial least in this PRECIS-2 score system. 

     6. Flexibility (Adherence) 

• This domain check if the protocol adherence and monitoring techniques are compatible with the real-life scenario or not. 
• Encouragement to take intervention in its defined dose and time is mandatory both in clinical trial as well as clinical practice. But physician can only encourage and convince patient about the adherence to the treatment in usual care settings but in clinical trial there might be need of monitoring tools to be applied just to verify that adherence to treatment is ensured.  
• If trialist apply monitoring tools for protocol adherence to treatment, trial will be inclined to explanatory and will score close to '0' in PRECIS-2 tool. Whereas, if there involve only the instructions and encouragement from researcher / physician for trial participants without applying any monitoring tools, that study will score close to '5' in PRECIS-2 tool. 
• Monitoring tools may include pre-screening evaluation of adherence, withdrawal of participants based upon cut-off value of intervention adherence, scheduling discussions and repeated questioning to study team etc. this approach leads study to be descriptive from pragmatic. 

     7. Follow Ups 

• This domain focus on the how different are the follow ups procedure set by trialist from that being practiced at the hospital / site on routine usual care settings. 
• If the trial is very pragmatic, there won't be any scheduled follow up for participant after being discharged. But measuring an outcome of an intervention may be difficult if it could not be derived from electronic means, medical records and registries. Those trials which have no or minimal follow ups and no additional information to be collected during follow ups are considered to be more pragmatic trials. Such trials tend to score close to '5' as per PRECIS-2 tools. 
• In explanatory trials like blinded study of vaccine candidates, there would be frequent scheduled follow ups, follow up visits may affect primary outcomes and there would be extensive study of various biological markers from blood and other samples. 

    8. Primary Outcomes

• This domain emphasizes if primary outcome expected from clinical trial is directly relevant to participant or not
• While designing the pragmatic trial, outcome set by the trial should solve the problem of the people attributed from disease or condition being studied. For example, if a trial aims to reduce mortality from disease, its primary outcome should be the number of death events among enrolled participants in the defined time period. Same applies if primary outcome is based upon biological marker or a surrogate marker. 
• In the best-case scenario, the drug or a therapy used in pragmatic trial in particular sites will be the standard of care in future globally. Those trials with an obvious importance to the participants, score highest (close to '5') in PRECIS - 2 whereas studies whose outcomes are not the part of routine care scores lowest. Such trials are considered to be more explanatory than pragmatic.

    9. Primary Analysis

• This domain typically considers if all the data generated via trials are being considered during analysis phase or not
• Almost all the pragmatic trials use Intention-to-treat analysis model where all the participants enrolled into the trial are equally considerable for statistical data analysis regardless of whether they received full treatment, meet the primary outcome or loss to follow up. Intention-to-treat model typically follows 'Once Randomized, Always Analyzed' hypothesis which provides them very high reproducibility than per protocol analysis trials. 
• It is not possible for all the trials to follow Intention-to-treat model, where they will consider only those data which has reached data integrity benchmark as set by the protocol for statistical data analysis. Such trials are considered to be explanatory which serves the propose of being high specificity when used in the mass scale. For example, during the time of COVID-19 pandemics, therapy trials followed pragmatic approach and vaccine trials majorly followed explanatory models. 

When should the PRECIS - 2 Tool Be Applied? 

Keeping it simple, PRECIS - 2 tool is designed for trialist to be implemented while developing the trial protocol. All the domains of tools are applicable only when there is sufficient room to anticipate the future scenario of usual care post trial and implement the study protocol accordingly. But sometimes, for knowledge purpose, PRECIS - 2 tool can be applied for those trials which are already in implementation phase. Findings from such studies can be inculcate by making an amendment to the protocol if study allows adaptive clinical trial design. 

How to Use PRECIS - 2 Tool? 

Trialist can visit and register their trial from official website of PRECIS - https://www.precis-2.org/. After receiving confirmatory email response from university of Aberdeen, they can move forward to follow the scoring system. 

   

      Thanks!!!

 

About Monkeypox Outbreak : All You Need To Know

Alert First !!! 

Nepal has reported its first ever case of Monkeypox infection on 20 Dec 2024 who was a migrant worker returned from Saudi Arabia on the previous day. This event has ignited an alert in the medical system as well as public domain in order to remain untouched from the disease of public health concern. Kindly read further in order to get more details ... 

On 23 July 2022 World Health Organization (WHO) has declared Monkeypox as global health emergency quoting the report released from second meeting of International Health Regulation (IHR). This declaration was based considering the views of committee members, advisors and reports of multi-country outbreak. In response different countries has alerted their respective health authorities to get prepared for yet another public health challenge. Since India recently has reported increasing new cases and death event of Monkeypox victim, Nepal is also at risk of this disease outbreak if not able to take effective action early on. As an initiative, WHO representative has recently handed PCR test kits required for Monkeypox diagnosis to National Public Health Laboratory (NPHL) Nepal. This effort officially initiated in-house capacity development for disease surveillance, case identification and containment activities which should be strengthen enough to sustain and take control over future outbreak.

Brief History Of Monkypox Outbreak

Caused by Orthopoxvirus, monkeypox - supposed to be shy on human has reported its first case against human on 1970 from Democratic Republic of Congo. Firstly identified in 1958 from laboratory Monkey, Monkeypox has two distinct genotypes - Congo Basin and West African. The First outbreak was noticed in these two geographic regions only with animal to human transmission as primary source of infection and human to human transfer as the disease further spread. Outside Africa, Monkeypox was reported in United States by 2003 in dogs which rapidly infected people of midwestern states such as Wisconsin, Indiana, Illinois, Kansas, Missouri and Ohio. With extensive diagnostic, isolation and treatment facility, US was able to contain the virus within a month of spread. After a long gap of 15 years, United Kingdom reported four cases of Monkeypox on human beings by 2018 from people who moved to UK from Nigeria. With rapid public health responses, UK also contained the virus. Similarly, such small incidents were being identified and subsided in various other countries like US, Israel, Singapore and Benin within 2018 to 2021. 

Unfortunately on recent outbreak started from UK, world has miserably failed to contain the spread of virus and it is taking its toll globally and spreading further. First cases of west African strain was identified on 6 May 2022, followed by six more such events within a week. As per High Consequences Infectious Disease (HCID) network, total of 1735 cases were already reported by mid July, most of which are centered around London. Virus has made its way throughout the Europe, America and our close neighbor India as well. 

Clinical Progression of Monkeypox Infection

• For initial 10 - 12 days, there is an incubation period 
• Prodromal symptoms of headache, fever, malaise, weakness etc. 
• Lymphadenopathy: Localized or general swelling of lymph nodes is the distinguishing clinical presentation of monkeypox from other infections
• Rashes develop very soon which further progress to well formed lesion. Initial macular rashes develops to papules, vesicles and pustules. Monekypox lesion are well circumscribed, deep and umblicated (a dot like pattern is noted on the top). 
• Lesions generally confined to facial, anorectal and genital regions, 
• Generally 2 - 4 weeks of infection, the pustules get crusted and scabbed over and the illness resolves. 

Monkeypox has distinct clinical features from viruses of similar kind Chickenpox and Smallpox. Chickenpox is much more contagious, rashes appeared in a wave fashion and get subsided by  two weeks. Smallpox mimics monkeypox to maximum degree but thankfully timely development of vaccine has eradicated it by 1980 already. 

Is Monkeypox More Prominent in LGBTQ community ? 

Recent report from WHO has suggested that 98 % of the monkeypox cases  outside Africa are reported in gay men. This fact has spread a message of LGBTQ community being targeted disease population which can be misleading and help disease to spread further. In fact, spread of disease is dependent on people's behavior, basic health practice and hygiene not the sexual orientation. Monkeypox can be transmitted by close personal contact which includes - direct skin to skin contact, contact with body fluids, touching infected objects used by victims such as towel, beddings and clothes; respiratory contact also helps in easy transmission of disease. Also infected mother transmit the disease to fetus as monkeypox virus can cross placental barrier. It implies that any kind of close physical intimacy is attributable to disease spread. Reason behind predominance of reports from gay and bisexual community may be their confined communication and intimacy among their own community and poor health / hygiene practice. In fact, LGBTQ is highly susceptible to other infections also where disease  transmission is directly linked with sexual contact.

Is Monkeypox  changing its disease pattern ? 

Recently on 1st of August 2022, India has reported its first death case of monkeypox. A 22 years young male was tested positive on 19 July in UAE, but he travelled to India and later developed fever and swelling  and admitted to hospital at Kerala state. Though patient was having lymphadenopathy and fever, there were no lesions noticed throughout stay. Patient's overall health status quickly deteriorated and succumbed to death. As per the autopsy report, cause of death was unconfirmed and other justifiable underlying medical illness were absent, cause of death was attributed to monkeypox.  Though World Health Organization (WHO) has officially labeled the disease as moderate public health risk, reported case fatality are  in increasingly trend. Comparing the classical clinical presentation with the recent deaths reported from India, Brazil and Spain, all death events seems to be unanticipated. Here, Clinical presentation of monkeypox are more or less similar but susceptibility of the victims to other various infections increased significantly after getting infected with monkeypox. This phenomenon is further augmented by underlying chronic illness. Since there are no new reported mutated variants, disease pattern of virus is still unchanged. 

Treatment and Prevention

• Medicines: As per the Food and Drug Administration (FDA), there are no approved treatment specific for monkeypox virus. However, treatment of smallpox and cytomegalovirus also works for Monekypox as well. A drug candidate named "Tecovirimat" has shown some promising results from animal studies but scant is known about it's effectiveness in human; further clinical trials are under the way. Other potential treatment candidates include VIGIV, cidofovir, Brincidofovir, for which also extensive effectiveness data is yet to come. 

• Vaccination: Pre-exposure prophylaxis in the form of vaccination is the currently available most effective way of disease prevention. For various reasons, Center for Disease Control and Prevention (CDC) has suggested only high risk personnel such as laboratory workers be get vaccinated against Orthopoxviruses which is effective against Smallpox as well as Monkeypox. Routine immunization for all health workers is not a current recommendation. The two FDA licensed vaccine candidates are JYNNEOS and ACAM2000. The former is to be taken in two dosage 28 days apart and later one in single dose. 

• Public Health Measures: Active surveillance, investigation and contact tracing is mandatory to prevent human to human transmission by rapidly identifying, isolation and treatment of infected individuals and halt the speed of new transmission. Along with these measures since transmission of monkeypox is somewhat similar to COVID-19 (not in intensity), common public health measures are also similar. Routine healthy practice includes avoiding unnecessary public gathering, wearing mask in public places, washing hands frequently, avoiding unhealthy sexual behaviors and avoiding pregnancy by suspected women. 

Is There A Chance of Monkeypox Pandemic ?

Considering all the reported information about the natural history of disease, Monkeypox can affect human life significantly by becoming a major public health concern for a particular point of time at its worst but resulting into pandemic is far beyond from its ability. There are many attributable factors needed to create pandemic such as rate of disease spread, mode of disease transmission, incubation period of disease, clinical severity, effectiveness of available treatment options and preparedness of health facility in different countries. Monkeypox stands with feeble strength in all these aspects. Firstly, transmission potential of Monkeypox is far more slower and weaker than any other pandemic we have witnessed (like smallpox, COVID-19 etc); in order to transmit disease, relatively longer close physical contact is needed which itself limits rapid spread of disease. Also clinical severity of the disease is very less since there is no systemic involvement of the virus, which makes death due to Monkeypox virus alone extremely unlikely. Also, if we suffice the availability of smallpox vaccine before the disease take over and make use of all the strengthened (and already sensitized) healthcare system and augment it little further, existing healthcare facility can easily withstand burden of this disease. 

Monkeypox will be a big burden only if respected health authority of the countries fail to implement common public health guideline suggested by experts. 

Thank You !!!

References: 

1. https://www.nepalitimes.com/banner/big-story-of-small-pox-in-nepal/

2. https://www.cdc.gov/poxvirus/monkeypox/clinicians/clinical-recognition.html#:~:text=Persons%20with%20monkeypox%20will%20develop,lymphadenopathy%20(swollen%20lymph%20nodes).

3. https://www.bbc.com/news/world-asia-india-62344928

4. https://www.bmj.com/content/378/bmj-2022-072410

5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157091/#:~:text=Between%20September%202017%20and%2031,region%20of%20Nigeria%20%5B16%5D.

6. India reports Asia's first monkeypox-related death; exact cause unconfirmed | The Times of Israel

7. https://www.who.int/southeastasia/news/detail/24-07-2022-enhance-surveillance--public-health-measures-for-monkeypox--who

Pragmatic Versus Explanatory Clinical Trial: Which One To Prefer ?

Researcher and scientist have been employing two major types of clinical trials in order to generate evidence  for an intervention: Pragmatic trial and explanatory trial. Pragmatic approach tests the effectiveness of any therapy in a real life scenario by incorporating an intervention into the routine clinical practice whereas explanatory trials always focus on generating evidences on efficacy of an intervention in an ideal condition. By its design, Pragmatic trial always dominate the reproducibility of study results in real world whereas explanatory trials are always more robust and carry more complexity technically as well as practically. In this article, we will explore the importance and need of both the types of designs in different circumstances. 

What Makes Pragmatic Trial Popular ?

• Flexible Inclusion / Exclusion criteria: If a participant has confirmatory diagnosis of an illness that we are interested in, there is high chance of him / her being enrolled into the study assuming ethical aspects of trials are constant. this opportunity of enrollment has been given by the flexible inclusion / exclusion criteria however factors which may affect the integrity of trial are taken into consideration beforehand. 
• Simple design with large sample size: Since pragmatic trials are aimed to see whether an intervention actually works or not in real life scenario, these are always being conducted in multiple sites on various countries so that effectiveness can be measured in different hospital settings. Since pragmatic trials designs are simple, easy to understand and any clinical person working in hospital setting can implement them, majority hospital sites will agree to participate which further strengthen the external validity and reproducibility of  the study result. 
• Heterogeneity: Due to embedded heterogeneity, pragmatic trials always try to involve maximum number of patients, treatments and clinical settings. Since heterogeneity itself can dilute the findings of the trial, very large sample size is designed for such trial which again provides opportunities of participation in trial even from resource limited countries like Nepal. 
• Intention to treat analysis: Since participants once randomized into the trial are always qualified for statistical data analysis, those participants who have enrolled into the trial but unable to complete the medication dose as well as loss to follow up before primary outcome was observed will also be contributing in evidence generation. 
• Controls the off lable use of potential candidates: After the COVID-19 outbreak, there were many potential candidates recommended from small studies and being used widespread but clear and strong evidence was lacking. Such 'off label' practice was discouraged rather a pragmatic clinical trial was designed which included as many hospital sites as possible. This practice was initially centered to United Kingdom which soon widespread throughout. 
• High External Validity: Being an open labeled and study not conducted in the controlled settings, the pragmatic trial results from the study population represent the target population in the future as well. This ability to generalize the findings in extended population is considered as high external validity. 

Current Upsurge Of Pragmatic Trial

Though scientific community was well acquainted with the term 'Pragmatic trial' since 1967, it was not the practice of choice for conducting any trial to see the effectiveness of any novel drug over the existing therapy or the placebo. Few terms like 'naturalistic', 'practical' and 'real life' are found to be used since then just to represent need of clinical trial that can be conducted in usual routine clinical settings as well - in short need of a pragmatic trial. Rise of COVID-19 pandemic not only ignited a fire to conduct clinical trials in clinical settings but also changed the pattern of ongoing pragmatic clinical trials. Countries with limited healthcare resource like Nepal also got an opportunity to participate for evidence generation only after globalizing certain pragmatic clinical trials such as RECOVERY (Randomized Evaluation of COVID-19 Therapy), ASCOT Adapt (Australiasian COVID -19 Trial), WHO Solidarity / Solidarity Plus Trial, REMAP - CAP (Randomized Embedded Multifactorial Adaptive Platform for Community Acquired Pneumonia) etc. 

Why explanatory trials are still surviving ? 

Though pragmatic trials recently gained popularity on resource limited clinical settings due to their flexible designs and easy implementation, explanatory trials are still more scientific and robust to demonstrate the efficacy of a particular therapy on a controlled setting. Here are few points which shows why we should not shift attention completely from such studies: 

• Drug discovery research: In order to develop a novel therapy via drug discovery research, blinded randomized controlled trial are needed where efficacy of a therapeutic agent is the only matter of concern for the researcher and all other aspects are kept constant. 
• Regulatory approval: For any drug or a vaccine or a therapy to bring into the market, regulatory approval is needed from the regulatory authority of the respective country. Food and drugs administration (FDA) as well as other regulatory agencies gives approval for the candidates studied via conventional explanatory clinical trials design only. 
• High Internal Validity: Explanatory trials have higher internal validity as they can better establish cause and effect relationship in inferential research than a pragmatic trial, hence dominates the hierarchy of evidence. 
• Reduced Bias: Few integral components of explanatory trials such as randomization, blinding, allocation concealment, stringent inclusion and exclusion criteria etc. plays a major role to control and minimize the systematic errors (biases) while same makes the trial harder in implementation. 
• Ambiguous "Real Life Settings": All the pragmatic trials throughout the globe are popular mainly because these are well fit into the real life setting. But real life settings of a country is completely different from other - such as United Kingdom and Nepal. Here, an exactly similar procedure (example: participant follow up) can be extremely easy for a developed nation with well established record keeping system whereas low income country (like Nepal) may wrestle with different mobile networks. 

Conclusion: 

Finally, both the trial methods have their own unique way of addressing the research question - Pragmatic trial answers in more flexible manner whereas explanatory trials search for evidence in a very controlled environment. Rise of COVID-19 pandemic has triggered scientific community to conduct pragmatic trials throughout the glove so that hospital operating on distinctly variable resource setting got opportunity to participate in a same trial. Such studies are important for development of new therapy whereas if a trial is being conducted in a new chemical entity or the relative risk of participants being negatively affected is higher, such trials should be conducted in explanatory manner.  Also if a trial is being conducted for sole purpose of marketing a new drug in the future, such studies are bound to be conducted in a controlled environment and regulatory authority of the respective country should have a close view to them. 

If you have any thoughts to share with public, Kindly mention in comment section below !!! 

 

Use of Placebo in Surgical Clinical Trials

Back in the 1950s, bilateral ligation of internal mammary arteries was treatment of choice for patients with angina pectoris. Doctor Cobb was skeptical about the effectiveness of this procedure hence, decided to compare a group of patients who underwent this surgery with another group of participants whom he performed all other procedures except ligating internal mammary arteries. Despite being ethically questionable, this study is considered to be the first documented placebo-controlled randomized double blinded clinical trial in surgery. Interestingly, it was later found that there was no significant improvement in patients due to this surgery compared to placebo. 

Comparing an intervention (medicine or surgical procedure) with a fake counterpart in order to check the superiority of intervention is the concept behind Placebo controlled studies. For any placebo controlled surgical trials, the procedure we perform should meet these two criteria: definition of surgery and the definition of placebo. Any medical intervention that involves changes in anatomy and requires skin incision or use of endoscopic procedures is surgical intervention. In order to fit with the definition of placebo, these surgeries should have been performed following all procedural aspects excluding actual penetration of intended anatomical structure. 

Surgical randomized trials are less commonly practiced in the research community. 

Steps of Performing Placebo Controlled Surgical Trials